Cyanopiperidines, especially 4-cyanopiperidine, are used as intermediates for the production of pharmacologically valuable substances like antidepressants, anti-inflammatory and immunomodulators. 4-Cyanopiperidine is also used as a starting material for the preparation of a large number of piperidine derivatives.
Several different conventional methods for producing cyanopiperidines are known.
U.S. Pat. No. 5,869,663 to Emonds-Alt et al., discloses a single step process for producing 4-cyanopiperidine from isonipecotamide (or piperidine-4-carboxamide) by dehydrating with phosphorous oxychloride, addition of concentrated mass to maintain pH—13, followed by multiple extractions with dichloromethane and ether. This process is laborious and is not commercially lucrative due to the involvement of multiple extractions with a mixture of low boiling solvents and generation of significant amounts of effluents. Moreover, the yield with above process is very low (approx. 25% w/w, 30% molar).
U.S. Pat. No. 4,284,636 to Carr et al., discloses the preparation of 4-cyanopiperidine by reacting piperidine-4-carboxamide with triflouroacetic anhydride and refluxing the reaction mass for 19 hours. Trifluoroacetic anhydride and trifluoroacetic acid are removed in vacuo and residual 4-cyano-1-fluoroacetyl piperidine is added to aqueous solution of potassium carbonate and methanol. Methanol is recovered and benzene is added to the concentrated reaction mass. Workup and distillation in vacuo gives the desired product 23%, w/w and 27% molar yield of 4-cyanopiperidine. The major drawbacks of this process are that it involves several steps, usage of hazardous chemicals, multiple solvents, generation of effluents and lower yields, thus, rendering the process industrially unattractive.
Therefore, there is a need to develop an improved process for producing cyanopiperidines, in particular 4-cyanopiperidine, which overcomes the disadvantages associated with the processes discussed above.